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21 pages, 6272 KB  
Article
Integrated Molecular and Functional Characterization of Cervical Small-Cell Neuroendocrine Carcinoma Using a 3D Organoid Model
by Hasibul Islam Sohel, Umme Farzana Zahan, Masako Ishikawa, Kosuke Kanno, Hitomi Yamashita, Kentaro Nakayama and Satoru Kyo
Int. J. Mol. Sci. 2026, 27(5), 2393; https://doi.org/10.3390/ijms27052393 - 4 Mar 2026
Abstract
Cervical small-cell neuroendocrine carcinoma (SCNEC) is a rare cervical cancer with high metastatic potential and is frequently associated with high-risk human papillomavirus (HPV) infection. Because of its low incidence, SCNEC remains understudied and treatment options are limited, posing major therapeutic challenges. This study [...] Read more.
Cervical small-cell neuroendocrine carcinoma (SCNEC) is a rare cervical cancer with high metastatic potential and is frequently associated with high-risk human papillomavirus (HPV) infection. Because of its low incidence, SCNEC remains understudied and treatment options are limited, posing major therapeutic challenges. This study aimed to characterize SCNEC at the molecular and functional levels to support more informed therapeutic strategies. Organoids and spheroids were generated from a cervical SCNEC biopsy, and a matched organoid-derived xenograft was established in immunodeficient mice. Model fidelity was evaluated by histopathology and immunohistochemistry. HPV status was assessed by p16 immunostaining and HPV18 PCR, and viral–host integration sites were inferred using whole-exome sequencing (WES) junction reads. WES was also used to compare shared somatic variants and copy-number alterations across the patient tumor, organoid, and xenograft. Drug responses were assessed in organoids and spheroids following exposure to a panel of chemotherapeutic agents and a targeted inhibitor. Organoids exhibited robust growth, morphologic maturation, and efficient recovery after cryopreservation. The organoids and matched xenografts faithfully recapitulated SCNEC, with preserved neuroendocrine differentiation (CD56, synaptophysin, and NSE positivity), a high Ki-67 proliferative index (>80%), and strong p16 expression. HPV18 status was conserved across the primary tumor, organoids, and xenografts, with an integration site at chr8 (8q24.21) associated with increased MYC expression. Whole exome sequencing (WES) revealed strong cross-model concordance, including 26 shared somatic variants with a canonical PIK3CA hotspot mutation (p.E542K) and conserved oncogenic copy-number gains of PIK3CA, TERT, and MYC, as well as copy number loss of TP53. Functional assays showed dose-dependent loss of viability following exposure to conventional cytotoxic agents or an mTOR pathway inhibitor. This study presents the first integrated molecular and functional analyses of patient tumors and matched organoid and xenograft models in cervical SCNEC. These models offer robust resources for mechanistic studies and may enable precision therapeutic strategies for this rare malignancy. Full article
(This article belongs to the Special Issue Genomics and Proteomics of Cancer)
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19 pages, 8550 KB  
Article
Screening of Maize Cultivars with Phytoremediation Coupled with Agro-Production for Cd Pollution in Farmland Soil
by Zongqing Wei, Dingyang Li, Hui Li, Lianfeng Du, Chuanjiang Peng, Rongli Tang, Jie Liu and Jing Liu
Agriculture 2026, 16(5), 588; https://doi.org/10.3390/agriculture16050588 - 4 Mar 2026
Abstract
Agricultural soil Cd (Cd) pollution threatens global food safety. Based on a meta-analysis of 55 global studies involving 464 maize cultivars, this research systematically elucidates the potential of maize for safe production and remediation in cadmium (Cd)-contaminated farmland. For low to moderately polluted [...] Read more.
Agricultural soil Cd (Cd) pollution threatens global food safety. Based on a meta-analysis of 55 global studies involving 464 maize cultivars, this research systematically elucidates the potential of maize for safe production and remediation in cadmium (Cd)-contaminated farmland. For low to moderately polluted fields, multiple cultivars with low grain Cd accumulation were identified, including 15 cultivars such as TieYan 919 and DanYu 508, which achieved over 90% lower grain Cd content than the legislative limits. DongDan 118 demonstrated simultaneous grain Cd reduction and yield increase, while XianYu 335 and ZhengDan 958 showed comprehensive performance in Cd reduction and yield stability. Maize genotype was identified as the decisive factor for grain Cd accumulation, soil pH was the key environmental factor regulating Cd translocation to grains, and field cultivation was conducive to the expression of low-accumulation traits. Accordingly, a “production coupled with remediation” technical pathway is proposed, centered on “low-accumulation cultivars as the core, soil pH regulation as the key, and field validation as the safeguard.” For heavily polluted fields, high-Cd-accumulating cultivars such as GuangTian-2 and JinZhuMi (pot cultivation) and HuaCaiNuo3 and QiuQing88 (field cultivation) were identified. Their remediation efficiency was driven by soil available Cd content, with significant local environmental influences, necessitating a remediation strategy guided by “cultivar selection as the core, soil management as the supplement, and local validation as the prerequisite.” This study provides a cultivar selection basis and agronomic regulation framework for the tiered management of Cd-contaminated farmland. Full article
(This article belongs to the Section Agricultural Soils)
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19 pages, 3591 KB  
Article
Latilactobacillus curvatus IM01 Alleviates Allergic Airway Inflammation Through Microbial and Metabolic Crosstalk Along the Gut–Lung Axis
by Yujia He, Jing Liu, Tao Yang, Yuanming Huang, Liqiong Song and Zhihong Ren
Nutrients 2026, 18(5), 834; https://doi.org/10.3390/nu18050834 - 4 Mar 2026
Abstract
Background: Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut–lung axis. While Latilactobacillus curvatus is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. Objective: In this study, we investigated [...] Read more.
Background: Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut–lung axis. While Latilactobacillus curvatus is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. Objective: In this study, we investigated the protective effects and underlying mechanisms of L. curvatus IM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach. Results: Our results demonstrated that oral administration of L. curvatus IM01 significantly attenuated airway inflammation, suppressed Th2-type immune responses, and reduced serum IgE levels. Crucially, our multi-omics integration revealed a coherent gut–lung axis narrative driven by microbial and metabolic crosstalk. Specifically, 16S rRNA sequencing indicated that L. curvatus IM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such as Odoribacter and Lactobacillus. This microbial restructuring was closely associated with a modulated cecal metabolic profile, as untargeted metabolomics exhibited a clear trend toward the restoration of key systemically active immunoregulatory metabolites, including indolelactic acid (ILA) and choline, which have been previously linked to the alleviation of AAI symptoms. Further linking this metabolic shift to respiratory immune tolerance, lung transcriptomic analysis showed that the treatment is strongly associated with the promotion of the differentiation of CD4+ T cells into Foxp3+ regulatory T cells (Tregs). Conclusions: Collectively, these findings suggest a novel potential pathway by which L. curvatus IM01 modulates the gut–lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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14 pages, 891 KB  
Systematic Review
Advanced Medical Therapies for Perianal Fistulizing Crohn’s Disease: A Systematic Review of Clinical, Radiological, Surgical, and Composite Outcomes
by Fares Jamal, Tayo Segun-Omosehin, Taylor Viggiano, Hamza Khan, Alejandro J. Gonzalez, Geoff Thomas, Sandra Elmasry and Talha A. Malik
Pharmaceuticals 2026, 19(3), 417; https://doi.org/10.3390/ph19030417 - 4 Mar 2026
Abstract
Background: Perianal fistulizing Crohn’s disease (CD) is associated with significant morbidity and remains difficult to treat. Although advanced medical therapies are widely used, much of the available evidence derives from heterogeneous fistula populations or luminal CD trials, with limited perianal-specific synthesis and [...] Read more.
Background: Perianal fistulizing Crohn’s disease (CD) is associated with significant morbidity and remains difficult to treat. Although advanced medical therapies are widely used, much of the available evidence derives from heterogeneous fistula populations or luminal CD trials, with limited perianal-specific synthesis and inconsistent outcome definitions. We conducted a systematic review focusing exclusively on perianal-specific clinical, radiologic, and composite outcomes in adults with perianal fistula (PAF) CD. Methods: We performed a systematic review in accordance with PRISMA 2020. Electronic databases were searched from inception through November 2025. We included randomized controlled trials and cohort studies enrolling adults with CD reporting outcomes specific to PAF. Interventions included biologics and small-molecule therapies, compared with placebo or other therapies. Due to substantial heterogeneity in outcome definitions and study designs, a meta-analysis was not performed. Risk of bias was assessed using Risk of Bias 2 (RoB 2) for randomized trials and the Newcastle–Ottawa Scale for observational studies. Results: Seven studies including >1200 participants with PAF-CD met inclusion criteria. Follow-up ranged from 24 weeks to 5 years. Across studies, outcome definitions and assessment modalities varied. Upadacitinib demonstrated significantly higher clinical fistula closure compared with placebo across multiple dose regimens at 52 weeks. In observational comparisons, ustekinumab and vedolizumab were associated with higher clinical closure rates than anti-TNF therapies. However, infliximab demonstrated higher closure rates than adalimumab as a first-line treatment. The definition for radiologic remission was less consistent across studies and often did not parallel clinical outcomes. Composite clinical–radiologic remission and response were reported in a limited number of studies, with filgotinib showing higher composite outcomes in comparison to placebo in a phase 2 trial. Surgical interventions, relapse outcomes, biomarkers [C-reactive protein (CRP)/fecal calprotectin (FCP)], and patient-reported outcomes were variably reported and not consistently significant across comparisons. Conclusions: Evidence for advanced therapies in PAF CD remains limited by heterogeneity in endpoint definitions, subjectivity in clinical observation, inconsistent radiologic reporting, and reliance on subgroup or observational comparisons. While anti-TNF therapy remains the most established option in guidelines, emerging data suggest significant benefits with ustekinumab, vedolizumab, and JAK inhibitors in selected patients. There is a need for PAF-specific, adequately powered randomized trials using standardized composite clinical and radiologic endpoints. Full article
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17 pages, 78428 KB  
Article
Assessment of Homologous Recombination System Gene Expression in Chemologically Induced Carcinogenesis In Vivo Models
by Matvey M. Tsyganov, Danna Zh. Bulatova, Anastasia A. Fedorenko, Dmitry M. Loos, Pavel E. Nikiforov, Irina A. Tsydenova, Aigerim A. Bayanbayeva, Zhansaya Sharipkhanova, Sofia S. Timoshenko and Marina K. Ibragimova
Curr. Issues Mol. Biol. 2026, 48(3), 275; https://doi.org/10.3390/cimb48030275 - 4 Mar 2026
Abstract
Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The [...] Read more.
Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens enables the modeling of tumor formation and the monitoring of changes in molecular genetic parameters. This approach is important for understanding how tumor cells adapt to genotoxic stress and for advancing the development of personalized cancer therapies. The objective of this study was to evaluate the expression of key homologous recombination system genes in a model of chemically induced carcinogenesis in mice. Materials and Methods: Male outbred ICR (CD-1) laboratory mice (n = 40) were used to study chemically induced carcinogenesis. The animals were divided into four groups: two control groups and two experimental groups, which received 3-methylcholanthrene (MC) or trichloroacetic acid (TCA). Tumor cells were identified by histological analysis of autopsy material using light microscopy after standard hematoxylin and eosin staining. RNA and DNA were extracted from cell suspensions using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), respectively. The expression levels of homologous recombination genes were assessed by RT-PCR and microarray analysis. Digital PCR was performed to assess chromosomal aberrations in the Brca1 gene. Results: Tumor formations were identified in laboratory animals two months after 3-methylcholanthrene. Histological analysis revealed morphological changes in a pleomorphic cell tumor, forming diverse, multidirectional fascicular and swirling structures, as well as large solid foci composed of markedly polymorphic spindle-shaped and epithelioid cells. Analysis of copy number aberrations in the examined samples showed that the frequency of Brca1 deletions was 60%, while 40% of animals had normal gene copy number. To further characterize the molecular changes, we assessed gene expression levels through expression microarray analysis. A total of 14 genes were hypoexpressed in the tumor compared to the normal tissue, with p < 0.05. A high level of differential expression was characteristic for Rad50, Rad51, Brca1, Brca2, and Pold4. Two genes, Rad52 and Bard1, exhibited increased expression levels. It was shown that as the tumor mass increased, so did the frequency of homologous recombination genes with hypoexpression. Conclusions: Our findings confirm that MC and TCA influence tumor formation and reveal that suppression of homologous recombination genes may contribute to this process. In addition, it has been established that as tumors progress, the expression of DNA repair genes declines and aberrant gene states accumulate. These data emphasize the importance of studying the state of DNA repair genes for the development of more effective strategies for cancer diagnosis and therapy. Full article
(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 3rd Edition)
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36 pages, 7147 KB  
Article
Standardized Photobiomodulation Dosimetry Targeting the Base of Calvarial Critical-Sized Defects for Bone Regeneration: A Preclinical RCT Comparing Flattop vs. Gaussian Beam Profiles, with or Without Bio-Oss®
by Reem Hanna, Wayne Selting, Vincenzo Cuteri, Giacomo Rossi, Alessandro Bosco, Laura Emionite, Michele Cilli, Emanuela Marcenaro, Federico Rebaudi, Marco Greppi and Stefano Benedicenti
J. Funct. Biomater. 2026, 17(3), 125; https://doi.org/10.3390/jfb17030125 - 4 Mar 2026
Abstract
Photobiomodulation (PBM) has shown promising potential to enhance bone regeneration; however, its optimal delivery parameters and interactions with osteoconductive scaffolds remain insufficiently defined. This preclinical study is the first to incorporate a pilot dosimetry evaluation to standardize 980-nm PBM delivery and ensure that [...] Read more.
Photobiomodulation (PBM) has shown promising potential to enhance bone regeneration; however, its optimal delivery parameters and interactions with osteoconductive scaffolds remain insufficiently defined. This preclinical study is the first to incorporate a pilot dosimetry evaluation to standardize 980-nm PBM delivery and ensure that effective irradiance reached the target surface of critical-size calvarial defects in mice. The primary aim was to evaluate the effectiveness of this novel 980-nm PBM protocol delivered using either flat-top (FT) or standard Gaussian (ST) handpieces in enhancing bone regeneration in critical-size defects (CSDs), both with and without Bio-Oss® grafting. A total of 120 adult mice were allocated into twelve experimental groups (n = 10 per group): untreated (control), Bio-Oss® alone, PBM alone, and PBM combined with Bio-Oss®, using either FT or ST handpieces, and evaluated at 30 and 60 days. Animals received 980 nm irradiation at 0.6 W (nominal power output–set on laser interface) in continuous-wave mode for 60 s, three times per week, for two consecutive weeks. Pilot dosimetry included power meter measurements to determine the therapeutic power reaching the defect surface area and temperature monitoring to ensure safe energy delivery. The dosimetry study demonstrated that, after accounting for the optical properties of mouse shaved skin and the Bio-Oss® graft covered with Bio-Gide® membrane, the effective irradiance reaching the base of the defect surface area was 1.131 W/cm2 for the FT handpiece and 0.413 W/cm2 for the ST handpiece. This dose was sufficient to induce significant regenerative effects. Histological, Masson’s trichrome, and immunohistochemical analyses for Runx2, OCN, GLI1, CD34, and CTSK were performed to characterize early and late osteogenic events. The combination of PBM and Bio-Oss® significantly accelerated bone regeneration compared with PBM alone, with the FT handpiece producing the most uniform and advanced osteogenesis. PBM enhanced progenitor activation, osteoblast differentiation, angiogenesis, matrix deposition, and late-stage remodeling, demonstrating a synergistic effect with the scaffold, whereas Bio-Oss® alone or defect alone showed limited early regenerative potential. These findings highlight the effectiveness of this novel standardized PBM dosimetry and uniform beam profile (FT), supporting their use as a foundation for future randomized controlled trials in craniofacial bone repair. Full article
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17 pages, 2977 KB  
Article
Strategically Designed Coaxial Electrospun Nanofibers of Polylactic Acid/Glycerol Monolaurate Hydroxypropyl-γ-Cyclodextrin Inclusion Compound with Sustained Release for Active Food Packaging
by Yan Zhang, Siyu Zhu, Guang Yang, Jiahui Duan, Yanyan Liu, Shuang Gao and Fengrui Li
Foods 2026, 15(5), 872; https://doi.org/10.3390/foods15050872 (registering DOI) - 4 Mar 2026
Abstract
Post-harvest deterioration in strawberries is an urgent and critical issue that requires significant attention. Glycerol monolaurate (GML), a broad-spectrum food-grade antimicrobial agent, faces limited applicability due to its poor water solubility. In this study, a confined encapsulation strategy was employed to encapsulate GML [...] Read more.
Post-harvest deterioration in strawberries is an urgent and critical issue that requires significant attention. Glycerol monolaurate (GML), a broad-spectrum food-grade antimicrobial agent, faces limited applicability due to its poor water solubility. In this study, a confined encapsulation strategy was employed to encapsulate GML within hydroxypropyl-γ-cyclodextrin (HPγCD), which improved the physicochemical properties of GML and enhanced its stability in the environment. The fiber morphology was observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), confirming the presence of a uniform, non-nodular core–shell structure. The Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) validated the successful encapsulation of GML within the cavity of HPγCD. Thermogravimetric analysis (TGA) demonstrated that the thermal stability of the core–shell system was significantly improved. In vitro release followed first-order kinetics (R2 = 0.9842), with 79.5% of GML released over 68 h. The DPPH and ABTS assays demonstrated that PLA/GML-HPγCD NF exhibited sustained radical scavenging activity (p < 0.05, ANOVA). Compared to GML-HPγCD NF, PLA/GML-HPγCD NF exhibited prolonged antibacterial activity against Escherichia coli and superior antifungal efficacy in strawberry preservation. Meanwhile, PLA/GML-HPγCD NF significantly reduced lesion diameter and weight loss while maintaining hardness, total soluble solids, and vitamin C content over 8 days of storage. In conclusion, these characteristics highlighted the potential of P/G-HPγCD NF as a promising active packaging material for extending the shelf life of perishable fruits. Full article
(This article belongs to the Special Issue Application of Plant Natural Products in Food Preservation)
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12 pages, 559 KB  
Article
Comparison Between Catheter-Directed Sclerotherapy and Surgical Removal of Large Ovarian Endometriomas: A Retrospective, Single-Center Observational Study
by Yun Soo Chung, Hae-Rim Kim, Jin Kyung Baek, Heeyon Kim, Bo Hyon Yun, Man-Deuk Kim, Yong Jae Lee and Seok Kyo Seo
J. Clin. Med. 2026, 15(5), 1959; https://doi.org/10.3390/jcm15051959 - 4 Mar 2026
Abstract
Background/Objectives: The treatment options for endometriosis vary depending on individual needs and clinical circumstances. To preserve ovarian reserve, ethanol catheter-directed sclerotherapy may be considered as a treatment option. We compared the efficacy of catheter-directed sclerotherapy with that of surgical removal for the [...] Read more.
Background/Objectives: The treatment options for endometriosis vary depending on individual needs and clinical circumstances. To preserve ovarian reserve, ethanol catheter-directed sclerotherapy may be considered as a treatment option. We compared the efficacy of catheter-directed sclerotherapy with that of surgical removal for the treatment of large ovarian endometriomas. Methods: This retrospective, single-center study was conducted at a tertiary care center. Patients diagnosed with ovarian endometriomas of >10 cm between 1 January 2019 and 5 December 2024 were included. Fifteen patients underwent catheter-directed sclerotherapy, and 69 underwent laparoscopic ovarian cystectomy or oophorectomy. The changes in ovarian cyst size, anti-Müllerian hormone levels, and cancer antigen 125 levels after six months of treatment were determined. Results: Before matched comparison, anti-Müllerian hormone levels decreased from 2.48 ng/mL to 1.11 ng/mL 6 months after surgical treatment. In the catheter-directed sclerotherapy group, anti-Müllerian hormone levels decreased from 1.33 ng/mL to 1.19 ng/mL. In the 1:1 matched comparison between the catheter-directed sclerotherapy and surgical groups, the anti-Müllerian hormone levels decreased by approximately −0.13 and −0.59 in the catheter-directed sclerotherapy and surgical groups, respectively. The relative reduction in the anti-Müllerian hormone levels was approximately −0.25 and −0.78 in the unilateral and bilateral ovarian surgery groups, respectively. In the surgical group, cyst size decreased to 0 cm six months after treatment, whereas CA-125 levels decreased from 62.10 U/mL to 11.20 U/mL. In the CDS group, cyst size reduced to 3.30 cm, whereas CA-125 levels decreased from 74.20 U/mL to 17.60 U/mL. Conclusions: Catheter-directed sclerotherapy preserves ovarian reserve more effectively than surgical treatment, even in cases of large endometriomas. It may be a promising treatment option for individuals with low anti-Müllerian hormone levels who are planning to conceive. Full article
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14 pages, 1290 KB  
Article
A Two-Track Model of Huntington’s Disease Pathology: Striatal Atrophy Mediates Maladaptive Immune Dysregulation
by H. Jeremy Bockholt, Jordan D. Clemsen, Bradley T. Baker, Vince D. Calhoun and Jane S. Paulsen
Int. J. Mol. Sci. 2026, 27(5), 2384; https://doi.org/10.3390/ijms27052384 - 4 Mar 2026
Abstract
Huntington’s disease (HD) is characterized by progressive striatal atrophy and complex proteomic changes in the central nervous system. Using the ultrasensitive Next-Gen Ultra-Sensitive Immunoassay (NULISA) proteomic platform, we analyzed cerebrospinal fluid (CSF) from 88 persons with HD to dissect the biological correlates of [...] Read more.
Huntington’s disease (HD) is characterized by progressive striatal atrophy and complex proteomic changes in the central nervous system. Using the ultrasensitive Next-Gen Ultra-Sensitive Immunoassay (NULISA) proteomic platform, we analyzed cerebrospinal fluid (CSF) from 88 persons with HD to dissect the biological correlates of gray matter loss. Our findings reveal a distinct “Two-Track” model of pathology. The first track, marked by the axonal damage protein neurofilament light chain (NEFL), showed a strong inverse correlation with putamen volume (Pearson r = −0.53, p < 0.001), reinforcing its utility as a proxy for structural neurodegeneration. The second track was defined by a positive association between the immune regulator TNFRSF8 (CD30) and putamen volume (Pearson r = 0.36, p < 0.001), reflecting a decline in active immune-regulatory signaling as striatal atrophy advances. Given its established role in immune modulation, TNFRSF8 was pre-specified for follow-up to further interrogate this neuro-immune axis. Crucially, TNFRSF8 maintained an independent association with striatal volume (Beta = 0.24, p = 0.008) even after controlling for NEFL, genetic burden (CAG-Age Product score), and sex. Supplementary analyses confirmed that this structural–immune axis is localized specifically to the striatum—showing no association with generic structural control regions—and is driven by CAG repeat length rather than chronological aging. Furthermore, bidirectional mediation analysis supported an atrophy-driven model, where striatal volume statistically mediates the relationship between genetic burden and downstream immune dysregulation (p = 0.010). These results demonstrate that maladaptive immune signaling is a distinct pathological correlate in HD, separable from general cytoskeletal damage. This dual-axis framework warrants evaluation in larger longitudinal and interventional studies to guide future biomarker-driven patient stratification and target engagement. Full article
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24 pages, 3929 KB  
Article
A Dual Quantum Dot Fluorescent Probe for Time-Resolved Chemometric Detection of Chloramphenicolin Pharmaceuticals
by Rafael C. Castro, Ricardo N. M. J. Páscoa, João L. M. Santos and David S. M. Ribeiro
Nanomaterials 2026, 16(5), 322; https://doi.org/10.3390/nano16050322 - 4 Mar 2026
Abstract
Dual-emission photoluminescence (PL) nanoprobes provide improved analytical performance to develop a reliable and sensitive sensing platform for quantifying chloramphenicol in pharmaceutical samples, thereby ensuring therapeutic efficacy and patient safety. In this work, a dual-emission PL sensing platform combining carbon dots (CDs) and AgInS [...] Read more.
Dual-emission photoluminescence (PL) nanoprobes provide improved analytical performance to develop a reliable and sensitive sensing platform for quantifying chloramphenicol in pharmaceutical samples, thereby ensuring therapeutic efficacy and patient safety. In this work, a dual-emission PL sensing platform combining carbon dots (CDs) and AgInS2 quantum dots (QDs) capped with mercaptopropionic acid (MPA) was developed for the quantitative determination of chloramphenicol, resorting to chemometric methods for data analysis. CDs, CdTe QDs, and AgInS2 QDs were synthesized and individually evaluated considering their photostability, PL response and kinetics of their interaction with the antibiotic. After this, two dual-emission probes, CDs/MPA-CdTe and CDs/MPA-AgInS2, were prepared and assessed based on the complementarity of their individual emission features. The obtained kinetic PL dataset was processed using unfolded partial least squares (U-PLS) in order to explore the multidimensional information of the dual-emission systems and to evaluate the performance of both sensing platforms. CDs/MPA-AgInS2 probe was demonstrated to be the most efficient sensing platform due to its better compromise between sensitivity and photostability, as well as its cadmium-free composition, allowing the implementation of a more environmentally friendly analytical methodology. The optimization of the U-PLS models involved the assessment of the kinetic acquisition time and different spectral regions. The results showed that reliable, sensitive and efficient quantification could be achieved within the first 5 min of interaction and using the full emission spectrum of the sensing probe. Additionally, different interaction mechanisms were observed for each nanomaterial in the combined probe, being static for the CDs/chloramphenicol interaction and dynamic for MPA-AgInS2/chloramphenicol interaction, which supports the synergetic behavior of the combined probe. The proposed methodology was effectively applied to commercial pharmaceutical formulations, yielding accurate results with good figures of merit. Therefore, this approach can be used as a relevant alternative to existing methodologies for a rapid, robust, and environmentally friendly method for chloramphenicol quantification. Full article
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18 pages, 872 KB  
Review
Memory Cells in Atopic Dermatitis: Paving the Way to Disease Modification
by Raquel Dominguez-Lopez, Carlos J. Aranda, Enrique Gómez-de la Fuente, Bibiana Pérez-García, Javier Perez-Bootello, Carlota Abbad-Jaime de Aragon, Álvaro González-Cantero and Emilio Berna-Rico
Int. J. Mol. Sci. 2026, 27(5), 2371; https://doi.org/10.3390/ijms27052371 - 3 Mar 2026
Abstract
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which persistence of immunological memory underlies disease recurrence and progression toward atopic comorbidities. Evidence indicates that pathogenic tissue-resident memory T cells (TRM), including Th2- and Th22-skewed subsets, among others, persist in both [...] Read more.
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which persistence of immunological memory underlies disease recurrence and progression toward atopic comorbidities. Evidence indicates that pathogenic tissue-resident memory T cells (TRM), including Th2- and Th22-skewed subsets, among others, persist in both lesional and clinically resolved skin and rapidly re-initiate inflammation through production of IL-4, IL-13, IL-22 and IL-31, promoting barrier dysfunction and pruritus. In parallel, circulating CLA+ memory T cells retain skin-homing capacity and contribute to flare reactivation, while IgG1+CD23 IL-4Rα+ type-2 memory B cells (MBC2) constitute a reservoir for high-affinity IgE production, linking cutaneous inflammation with allergic comorbidities. These adaptive memory compartments are sustained by epithelial alarmins, dendritic cell–derived chemokines such as CCL17, CCL22 and CCL18, and the OX40/OX40L costimulatory pathway, which promotes differentiation, survival and tissue retention of memory T cells. Clinical and transcriptomic studies show how, although IL-4/IL-13 blockade reduces circulating type-2 responses, Th2A cells, Tc2 cells and activated dendritic cells can persist in clinically resolved skin, providing a mechanistic basis for relapse after treatment withdrawal. Together, these findings support the relevance of targeting memory-imprinting pathways as a promising mechanism to achieve durable disease modification in AD. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (3rd Edition))
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20 pages, 2227 KB  
Article
ATR Blockade Potentiates the Effects of Genotoxic Agents In Vitro and Promotes Antitumor Immunity in a Mouse Model of Non-Small Cell Lung Cancer
by Dimitra Mavroeidi, Christina Papanikolaou, Elisavet Deligianni, Panagiotis Malamos, Panagiota Stamou, Konstantinos N. Syrigos and Vassilis L. Souliotis
Cancers 2026, 18(5), 820; https://doi.org/10.3390/cancers18050820 - 3 Mar 2026
Abstract
Background/Objectives: Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer, and its main treatments include chemotherapy with genotoxic drugs and immunotherapy. Central to the cellular response to genotoxic stress is the DNA damage response (DDR) network, regulated by key [...] Read more.
Background/Objectives: Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer, and its main treatments include chemotherapy with genotoxic drugs and immunotherapy. Central to the cellular response to genotoxic stress is the DNA damage response (DDR) network, regulated by key kinases such as ataxia-telangiectasia mutated and Rad3-related (ATR). Herein, we tested the hypothesis that inhibition of ATR enhances the cytotoxicity of genotoxic agents and the antitumor immune response. Methods: DDR-related parameters and redox status, expressed as GSH/GSSG ratio, and apurinic/apyrimidinic lesions, were evaluated in human (A549, H1299) and murine (LLC) NSCLC cell lines after co-exposure to ATR inhibitor (AZD6738) and ultraviolet C (UVC) irradiation or cisplatin. Using a syngeneic LLC model, treatments of AZD6738 alone or in combination with cisplatin and/or anti-programmed cell death 1 antibody (anti-PD1) were examined. Results: In all cell lines, combined treatment with AZD6738 and cisplatin or UVC irradiation markedly decreased cell viability, DNA repair efficiency, and GSH/GSSG ratios; increased drug-induced DNA damage; and augmented apurinic/apyrimidinic lesions. In vivo, following treatment with AZD6738 and cisplatin, flow cytometry analysis performed in tumor cells revealed an increased infiltration of CD3+ and CD8+ T cells, with the triple combination of AZD6738, cisplatin, and anti-PD1 achieving the strongest antitumor effect. The CD3+CD4CD8 double-negative (DN) T cell population in tumor samples also emerged as a contributing factor in this context. Conclusions: These results demonstrate that ATR blockade concurrently enhances the efficacy of genotoxic agents and immune checkpoint inhibitors, thus paving the way for combination therapies in NSCLC. Full article
(This article belongs to the Special Issue Clinical Trials and Outcomes for Non-Small Cell Lung Cancer)
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12 pages, 606 KB  
Communication
Effects of Probiotic Lacticaseibacillus paracasei NSMJ27 on Laying Performance and Gut Health Indicators in Aged Laying Hens
by Viet Anh Vu, Yoo-Bhin Kim, Soo-Ki Kim, Ji Young Jung, Sang Seok Joo, Byeongcheol Ban, Myunghoo Kim, Minji Kim and Kyung-Woo Lee
Animals 2026, 16(5), 792; https://doi.org/10.3390/ani16050792 - 3 Mar 2026
Abstract
This experiment was designed to determine the effect of the Lacticaseibacillus paracasei (paracasei) strain NSMJ27, isolated from Korean fermented vegetable food (home-made kimchi), on laying performance, egg quality, intestinal histology, cecal short-chain fatty acids, and ileal antioxidant/immunity indicators of laying hens. [...] Read more.
This experiment was designed to determine the effect of the Lacticaseibacillus paracasei (paracasei) strain NSMJ27, isolated from Korean fermented vegetable food (home-made kimchi), on laying performance, egg quality, intestinal histology, cecal short-chain fatty acids, and ileal antioxidant/immunity indicators of laying hens. Ninety-six 55-week-old Hy-Line Brown hens were randomly assigned to two dietary treatments with each treatment comprising eight replicates of six hens each. Experimental diets were prepared by mixing corn and soybean meal basal diets without or with L. paracasei NSMJ27 at 2.5 × 109 CFU/kg. The experiment lasted 4 weeks. Laying hens fed with the NSMJ27-supplemented diet were not affected (p > 0.05) in their laying performance or egg quality. With respect to ileal morphology, villus height: crypt depth ratio tended to be higher (p = 0.067) in laying hens fed with L. paracasei NSMJ27 vs. control diets. Dietary L. paracasei did not affect (p > 0.05) the activities of glutathione peroxidase and catalase, malondialdehyde contents, or secretory immunoglobulin A in ileal mucosa, but increased (p = 0.048) the activity of superoxide dismutase compared with the control diet-fed laying hens. Dietary L. paracasei elevated (p = 0.016) the relative percentage of butyrate but lowered (p = 0.057) that of isovalerate in cecal digesta. Dietary L. paracasei did not affect the percentages of cells expressing macrophages, B cells, CD4+ T cells, CD8+ T cells, or TCRγδ T cell surface markers (p > 0.05). Overall, these results suggest that dietary L. paracasei NSMJ27 could enhance gut health via increasing gut antioxidant capacity and butyrate production in the cecal digesta of laying hens. Full article
(This article belongs to the Collection Application of Antibiotic Alternatives in the Poultry Industry)
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22 pages, 7407 KB  
Article
Hyperspectral Unmixing-Based Remote Sensing Inversion of Multiple Heavy Metals in Mining Soils: A Case Study of the Lengshuijiang Antimony Mine, Hunan Province
by Xinyu Zhang, Li Cao, Jiawang Ge, Ruyi Feng, Wei Han, Xiaohui Huang, Sheng Wang and Yuewei Wang
Remote Sens. 2026, 18(5), 767; https://doi.org/10.3390/rs18050767 - 3 Mar 2026
Abstract
Soil heavy metal contamination in mining areas poses a serious environmental challenge, requiring monitoring approaches with both wide coverage and high accuracy. Hyperspectral remote sensing provides an effective solution, yet its performance in complex mining environments is often limited by mixed-pixel effects and [...] Read more.
Soil heavy metal contamination in mining areas poses a serious environmental challenge, requiring monitoring approaches with both wide coverage and high accuracy. Hyperspectral remote sensing provides an effective solution, yet its performance in complex mining environments is often limited by mixed-pixel effects and nonlinear spectral responses. To address these issues, this study proposes a Physically-Constrained Collaborative Endmember Extraction (PCCEE) framework that integrates spectral unmixing with machine learning for multi-element inversion. Using Gaofen-5 hyperspectral imagery, a collaborative workflow combining Pixel Purity Index (PPI), Vertex Component Analysis (VCA), and prior-spectral-constrained Spectral Angle Mapper (SAM) was developed to improve endmember purity and physical interpretability. Among three unmixing models (LMM, NMF, and SVR), the Linear Mixing Model achieved the best balance between accuracy and efficiency. Random Forest regression using retrieved abundances enabled high-accuracy inversion of eight heavy metals (mean R2 = 0.85). Spatial analysis revealed significant co-enrichment of Pb, Cd, and Zn related to sulfide weathering, while PCA distinguished compound and independent pollution sources. The proposed PCCEE framework effectively mitigates mixed-pixel interference and provides a transferable approach for heavy metal monitoring and risk assessment in complex mining environments. Full article
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15 pages, 5144 KB  
Article
Imprinted Proteins as a Receptor in Fluorescent Sensing Microplate Assay for Herbicide Determination
by Kirill Y. Presnyakov, Ivan S. Matlakhov, Ivan A. Reshetnik, Polina M. Ilicheva, Daria V. Tsyupka, Daria G. Koganova, Svetlana A. Mescheryakova, Tatyana Y. Rusanova, Mikhail V. Pozharov, Daniil D. Drozd, Pavel S. Pidenko, Irina Y. Goryacheva and Natalia A. Burmistrova
Biosensors 2026, 16(3), 149; https://doi.org/10.3390/bios16030149 - 3 Mar 2026
Abstract
The manuscript describes an optical sensing microplate for the high-throughput screening of imidazolinone herbicides in soil extracts. As far as we know, imprinted proteins (IPs) specific to imidazolinone herbicides have not been synthesized and used as a recognition element for their solid-phase extraction [...] Read more.
The manuscript describes an optical sensing microplate for the high-throughput screening of imidazolinone herbicides in soil extracts. As far as we know, imprinted proteins (IPs) specific to imidazolinone herbicides have not been synthesized and used as a recognition element for their solid-phase extraction before. Imprinted bovine serum albumin (BSA) and glucose oxidase (GOx) were synthesized in the presence of imazamox as a template and then these IPs were immobilized at the bottom of microplate wells. The sorption capacity (Q) of aminated silica nanoparticles modified by IPs (IP–BIS) was 6.38 mg g−1 while the imprinting factor (IF) equaled 2.6. The concentration of imazamox was determined by a “turn-off” solid-phase assay using alloyed CdZnSeS/ZnS quantum dots (QDs) as a component of fluorescent substrate. Alloyed CdZnSeS/ZnS QDs were stabilized in an aqueous phase by positively charged cysteamine that, as far we know, had not been used as this type of ligand before. Our method allows for determining the concentration of imazamox in the range of 0.5–9.2 μg mL−1, with a limit of quantification limit of quantitation (LOQ) equal to 0.45 μg mL−1 The sensing microplate enables parallel detection of up to 96 samples containing herbicides using standard fluorescence microplate readers or smartphones. The paper describes how such sensing microplates can be used for the analysis of artificially contaminated soil samples. The proposed approach combines pre-concentration of analyte at the IPs with its subsequent determination on a single analytical platform, thus allowing for both highly sensitive determination in laboratory conditions and mass screening in the field. Full article
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